Over many years, various attempts have been made to utilise the respiratory tract as a means to deliver non-living vaccine antigens. This route was seen as conferring advantages in terms of vaccine acceptability (avoiding “needle phobia”), the opportunity to induce local immune responses and the potential to induce responses at distant mucosal sites given the assumed unity of the mucosal immune system. Much attention has been given to delivering vaccines by the intranasal route in humans and animals. Results to date indicate that this route requires very high antigen doses and/or the use of specialised delivery technologies to ensure antigen uptake and immune induction.
Similarly, delivery of vaccines via the intra-lung or pulmonary route has in the past generally required specialised delivery techniques, such as microencapsulation (see, for example, Oya Alpa et al., 2005), in order to optimise immune responses.
In work leading to the present invention, the inventors have observed that delivery of vaccines by the intranasal route is highly inefficient, inducing poor local immunity even at high antigen doses. Accordingly, the inventors have investigated an alternative route of vaccine administration which retains the advantage of avoiding “needle phobia”.
Surprisingly, the inventors have demonstrated the superiority of vaccine delivery to the lung over that by the intranasal route as a means of inducing immune responses. They have also demonstrated that strong systemic immune responses can be induced using very small quantities of antigen when delivered with adjuvant via the lung. In particular, the inventors have shown that a straightforward vaccine composition combining antigen and adjuvant induces strong systemic immune responses on intra-lung delivery without the need for specialised uptake technologies. Significantly, it has been shown that intra-lung delivery results in lung mucosal immune responses, which can be as much as one hundred-fold (100×) greater than that induced by conventional parenteral immunisation, even when very small quantities of antigen are delivered with adjuvant via the lung.
Griffith et al (1997) describe the intratracheal delivery of ricin toxoid formulated either in liposomes, with aluminium hydroxide or in PBS. The liposome formulated group showed best protection; aluminium hydroxide did not improve protection over PBS. WO 2005/110379 describes the pulmonary delivery of a particulate malaria vaccine. The formulation was delivered as a particulate formulation and permitted sustained release of antigen.
The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.
Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.